Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis.

OBJECTIVES: Acute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk. We performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19. METHODS: Relevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, IL-1, coronavirus, COVID-19, SARS-CoV-2. Trials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19 were included. RESULTS: Nine studies (n = 1119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio (OR): 0.38, 95% CI: 0.17-0.85, P = 0.02, I2 = 67%; six studies, n = 587) and mortality risk (OR: 0.32, 95% CI: 0.23-0.45, P < 0.00001, I2 = 0%; nine studies, n = 1119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0.75, 95% CI: 0.48-1.16, P > 0.05, I2 = 28%; five studies, n = 591) and bacteraemia (OR: 1.07, 95% CI: 0.42-2.73, P > 0.05, I2 = 71%; six studies, n = 727). CONCLUSIONS: Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.

Sinus Bradycardia Associated with Remdesivir Treatment in COVID-19: A Case Report and Literature Review.

BACKGROUND: Although remdesivir treatment is widely used during the pandemic coronavirus disease 2019 (COVID-19), there is scarce evidence regarding its cardiac side effects. CASE PRESENTATION: We report the case of a 36-year-old male hospitalized due to severe COVID-19 symptoms. He presented with a 10-day history of fever (up to 39.7 °C), productive cough, hemoptysis, fatigue, myalgias and hypoxemia. The patient received supplemental oxygen, dexamethasone, remdesivir and empirical antibiotic treatment according to protocol. Asymptomatic sinus bradycardia developed on hospital day 3 (namely, heart rate 39/min compared to 92/min on admission). Secondary causes of bradycardia were excluded based on the absence of relevant evidence from laboratory work-up and echocardiographic examination. The patient's rhythm restored to normal 9 days after the discontinuation of remdesivir. CONCLUSIONS: Considering the frequent use of remdesivir in patients with COVID-19, physicians should be aware of this possible adverse event.

Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019?

Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its host-cell entry through the disruption of lipid rafts or by inhibiting its replication. Available human studies have shown beneficial effects of statins and PCSK9 inhibitors on pneumonia and sepsis. These drugs may act as immunomodulators in COVID-19 and protect against major complications, such as acute respiratory distress syndrome and cytokine release syndrome. Considering their antioxidative, anti-arrhythmic, antithrombotic properties and their beneficial effect on endothelial dysfunction, along with the increased risk of mortality of patients at high cardiovascular risk infected by SARS-CoV-2, statins and PCSK9 inhibitors might prove effective against the cardiovascular and thromboembolic complications of COVID-19. On the whole, randomized clinical trials are needed to establish routine use of statins and PCSK9 inhibitors in the treatment of SARS-CoV-2 infection. In the meantime, it is recommended that lipid-lowering therapy should not be discontinued in COVID-19 patients unless otherwise indicated.